To characterize the clinical pharmacology of a given agent we take the following step-wise approach: development of an analytical method for quantitation in biological fluids; characterization of pharmacokinetics; pharmacokinetic modeling to govern future dosing schedules; evaluation of plasma protein binding; determination of renal elimination; in vitro metabolism studies to characterize the enzymes involved, metabolites formed and possible drug-drug interactions; development of pharmacodynamic correlations with efficacy and/or toxicity; pharmacogenetic approaches to further understand factors responsible for interindividual differences. Our research efforts have focused primarily on agents that target the aberrant biology of neoplasms (agents that target signal transduction pathways, angiogenesis inhibitors, cell cycle inhibitors, protein kinase inhibitors, antagonists of peptide growth factors) and on novel ways of administering cytotoxic agents.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010627-02
Application #
7292916
Study Section
(MOB)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Aragon-Ching, Jeanny B; Ning, Yang-Min; Chen, Clara C et al. (2009) Higher incidence of Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration resistant prostate cancer treated with anti-angiogenic agents. Cancer Invest 27:221-6
Sissung, Tristan M; Danesi, Romano; Price, Douglas K et al. (2008) Association of the CYP1B1*3 allele with survival in patients with prostate cancer receiving docetaxel. Mol Cancer Ther 7:19-26
Sissung, Tristan M; Gardner, Erin R; Gao, Rui et al. (2008) Pharmacogenetics of membrane transporters: a review of current approaches. Methods Mol Biol 448:41-62
Gardner, Erin R; Ahlers, Christoph M; Shukla, Suneet et al. (2008) Association of the ABCG2 C421A polymorphism with prostate cancer risk and survival. BJU Int 102:1694-9
Sharifi, Nima; Dahut, William L; Figg, William D (2008) The genetics of castration-resistant prostate cancer: what can the germline tell us? Clin Cancer Res 14:4691-3
Sissung, Tristan M; Baum, Caitlin E; Deeken, John et al. (2008) ABCB1 genetic variation influences the toxicity and clinical outcome of patients with androgen-independent prostate cancer treated with docetaxel. Clin Cancer Res 14:4543-9
Smith, N F; Baker, S D; Gonzalez, F J et al. (2008) Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100. Br J Cancer 98:1630-2
Wang, Weixin; Figg, William D (2008) Secondary BRCA1 and BRCA2 alterations and acquired chemoresistance. Cancer Biol Ther 7:1004-5
Beverage, Jacob N; Sissung, Tristan M; Sion, Amy M et al. (2007) CYP2D6 polymorphisms and the impact on tamoxifen therapy. J Pharm Sci 96:2224-31
Deeken, John F; Figg, William D; Bates, Susan E et al. (2007) Toward individualized treatment: prediction of anticancer drug disposition and toxicity with pharmacogenetics. Anticancer Drugs 18:111-26

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